GREM1 (Gremlin 1)

Integrated multi-omics analysis indicated that Gremlin-1 (GREM1) acts as a key regulator within the differential screening-selected gene aberrant in neuroblastoma (DAN) family genes-mediated transforming growth factor-beta (TGF-β) signaling pathway. In conclusion, our data establish a molecular classifier that stratifies patients into distinct score groups, with those in the low-CMLS group potentially benefiting from treatment with pilaralisib.

The expression of LGR5, BMI1, CDKN1B, and YAP/TAZ was comparable in untreated and CRT rectal cancer. The uniform expression of mesenchymal niche factors might prevent the zonation of the stem cell niche in rectal cancer.

Conversely, Grem1 heterozygosity combined with Spp1 knockout resulted in wild-type PDAC histology, a result that confirmed the direct antagonistic functions of these factors. Hence, mesenchymal and epithelial PDAC cell fates are determined by the reciprocal paracrine regulation of the soluble factors GREM1 and SPP1.

Our spatial analysis reveals intratumoural heterogeneity of TGF/BMP signalling and its significance for PDAC progression. Notably, stromal TGF-B2 emerges as a prognostic biomarker, while TGF-B1 and ID1 are implicated in adverse clinical and pathologic features. These findings highlight the importance of TGF/BMP signalling niches in the TME with implications for PDAC biology and can inform the development of future therapeutic strategies.

This article will summarize current knowledge of BMP and GREM1 regulation of CSC function, as well as conflicting data on the exact role of GREM1 in modulating CSC biology, tumor formation and cancer. Targeting this pathway by inhibiting GREM1 using neutralizing antibodies or small molecules may hold early-stage promise for novel therapeutic strategies aimed at reducing CSC burden in cancers and improving patient outcomes.

BMP inhibitor significantly promoted GREM1 expression and migration in BGC cells, but not GES-1 cells. GREM1 might serve as a potential and promising prognostic biomarker for drug development and cancer treatment.

A comprehensive analysis indicates that GREM1 is crucial in LUAD progression, with its overexpression predicting poor prognosis. GREM1 could be a potential therapeutic target for LUAD, providing insights for personalized therapy optimization.

Elevated GREM1 secretion inhibits the BMP/SMAD1/5/SMAD4 signaling cascade in OPCs, which inhibits oligodendrogenesis and myelination. These findings indicate the importance of endothelial cell-intrinsic PD-1 in regulating the oligovascular niche, and suggest potential therapeutic implications for neurological disorders associated with disrupted vascular development.

Spatial analysis of tumor-stromal interfaces across multiple GCs highlighted new ecosystem states not attributable to mere tumor/stroma admixture, landmarked by increased GREM1 expression. Our results provide insights into how the cellular ecosystems of individual GCs are sculpted by tumor intrinsic and extrinsic selective pressures, culminating in individualized patient-specific cancer cartographies.

We identified selective activation of ERK/MEK targeted inhibitors in cancer cells compared to HOSEs. This study offers insights into the normal and malignant ovarian cells, shedding light on cancer development and drug responses.

The pilot exploratory CTCs transcriptomics analysis showed transcriptional changes linked to cell proliferation such as under expression of MALAT1 and overexpression of GREM1, GPR85 and OCM. Our data underline the potential of an integration between ctDNA and CTCs, both through quantification and transcriptomic analysis, for a deeper understanding of tumor biology and treatment response in HR-positive, HER2-negative MBC.

High GREM1 expression was associated with sensitivity to cisplatin, docetaxel, gemcitabine, and vinblastine. Thus, GREM1 can predict prognosis and responses to immunotherapy and chemotherapy in BC patients, making it a potential biomarker and therapeutic target.